A new antisense oligonucleotide delivery system based on self-assembled ODN-PEG hybrid conjugate micelles

J Control Release. 2003 Dec 5;93(2):183-91. doi: 10.1016/j.jconrel.2003.07.002.

Abstract

The conjugate of antisense c-raf oligonucleotide (ODN) and poly(ethylene glycol) (PEG) was synthesized for intracellular ODN delivery. When combined with polyethylenimine (PEI), the ODN-PEG conjugate self-associated to form polyelectrolyte complex micelles in aqueous solution. The effective hydrodynamic diameter of the micelles was ca. 70 nm with a narrow size distribution. Flow cytometry analysis indicated that the cellular uptake of the micelles by A2780 cells was much higher than that of ODN alone. The micelles also showed a superior antiproliferative activity against ovarian cancer cells in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology*
  • Electrolytes / chemistry
  • Humans
  • Injections, Intralesional
  • Injections, Subcutaneous
  • Mice
  • Mice, Nude
  • Micelles*
  • Neoplasm Transplantation / methods
  • Oligonucleotides, Antisense / chemical synthesis
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / pharmacology*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology*
  • Polyethyleneimine / chemical synthesis
  • Polyethyleneimine / chemistry
  • Polyethyleneimine / pharmacology
  • Proto-Oncogene Proteins c-raf / chemistry
  • Proto-Oncogene Proteins c-raf / metabolism
  • Proto-Oncogene Proteins c-raf / pharmacology
  • Solutions
  • Time Factors

Substances

  • Drug Carriers
  • Electrolytes
  • Micelles
  • Oligonucleotides, Antisense
  • Solutions
  • Polyethylene Glycols
  • Polyethyleneimine
  • Proto-Oncogene Proteins c-raf